ANTI-PROLIFERATIVE ACTIVITIES OF VIETNAMESE HERBS

ANTI-PROLIFERATIVE ACTIVITIES OF VIETNAMESE HERBS

Van Khoa Vu *, Thi Giang An Nguyen, Thi Minh Chau Dao, Thi Huong Le, Thi Thao Do, Ngoc Hoa Nguyen, Thi Huong Lien Nguyen, Huu Thang Nguyen, Thi Hong Van Nguyen, Ngoc Dai Do, Huy Hung Nguyen and William N. Setzer

Surgeon of Orthopedic and Trauma, Deputy Department of Orthopedic and outpatient treatment, Vietduc University Hospital, Add: No. 40 Trang Thi Str., Hoan Kiem Dist., Hanoi, Vietnam.

ABSTRACT: Cancer is a dangerous global disease and causes a heavy economic burden in low-income countries. Traditional medicinal plants play an important role in the research and development of cancer treatment drugs. Twenty-four traditional Vietnamese herbs were evaluated for their cytotoxic activities against nine cancer cell lines including HepG2, A549, MCF7, HT-29, HeLa, RD, LNCaP, HL-60 and NTERA-2. Cytotoxic activity was assessed following Monks' protocol (1991) by measuring total cellular protein content using sulforhodamine B (SRB) staining. The 70% ethanol extract of eight medicinal herbs including Phyllanthus urinaria L. (TD.MD1), Solanum trilobatum L. (TD.MD2), Angelica sinensis (Oliv.) Diels (TD.MD3), Xanthium strumarium L. (TD.MD11), Scutellaria baicalensis Georgi (TD.MD15), Platycodon grandiflorus (Jacq.) A.D.C. (TD.MD17), Lycopodium clavatum L. (TD.MD20) and Ophiopogon japonicus (Thunb.) Ker Gawl. (TD.MD21) showed cytotoxic activity against HepG2, A549, MCF7, HT-29, HeLa, RD, LNCaP, HL-60 cell lines with IC₅₀ values ranging from 18.60 to 93.84 µg/mL. The hexane, ethyl acetate, n-butanol, water extract residues of the 70% ethanol extracts demonstrated cytotoxic activities against NTERA-2 cell line with IC₅₀ values of 8.60 to 90.83 µg/mL. This is the first study to evaluate the proliferation inhibition potential of these medicinal herbs on cancer stem cells. The eight medicinal herbs have shown potential to aid in the treatment of various cancers and as raw materials for further research on secondary metabolites with cytotoxic activity.

Keywords: Cytotoxic activity, Vietnamese herb, medicine plant, NTERA-2

INTRODUCTION: Cancer stands as a prominent contributor to global morbidity and mortality, with approximately 14 million new cases annually.

Projections indicate a staggering 70% surge in new cases over the next two decades. It ranks as the second leading cause of death worldwide, accounting for nearly one in every six deaths. Alarmingly, about 70% of cancer-related fatalities transpire in low- and middle-income nations ¹. In 2020, approximately 10 million deaths related to cancer were reported, solidifying its position as one of the primary causes of death worldwide ². Cancer stem cells (CSCs) are identified as a small population of tumor cells containing self-renewing and differentiating properties, they have the ability to initiate and proliferate tumors as well as metastasize and recur. More seriously, CSCs demonstrate drug resistance and overcome radiotherapy. It has been hypothesized that cancer stem cells (CSCs) are responsible for drug resistance and that targeting their treatment will lead to tumor regression ³.

Therefore, CSCs have become an important target for cancer treatment. Due to their high expression of stem signals such as Nanog homeobox, octamer-binding transcription factor 4, SRY-box 2, and teratocarcinoma-derived growth factor 1, NTERA-2 cells are widely utilized for assessing the anti-cancer stem cell (CSC) targeted activity of various compounds ⁴. Human embryo carcinoma cell line NTERA-2 has been proposed as an in-vitro test system for developmental neurotoxicity ⁵.

Using medicinal plants to inhibit the proliferation of cancer cell lines has received special attention from scientists. Natural compounds have been included as part of approved anti-cancer treatments ⁶. In this study, we evaluated the cytotoxic activities of 24 Vietnamese traditional medicinal herbs against 9 cancer cell lines including HepG2, A549, MCF7, HT-29, Hela, RD, LNCaP, HL-60 and NTERA-2. This study was conducted with the purpose of screening medicinal herbs with cytotoxic activity to support further research on herbal formulas supporting cancer treatment.

MATERIALS AND METHODS:

Cell Lines: The NTERA-2, A549, and various cancer cell lines (HepG2, A549, MCF7, HT-29, Hela, RD, LNCaP, HL-60) were provided as a gift by Dr. Prof. Wongtrakoongate from Mahidol University, Thailand, and Prof. J. Maier from Milan University, Italy.

Chemicals and Herbal Materials: Chemicals used in the cytotoxicity assay (sulforhodamine B, dimethyl sulfoxide, trichloroacetic acid, ellipticine) were purchased from Sigma-Aldrich. The solvents (n-hexane, ethanol, ethyl acetate, n-butanol) and other chemicals met analytical standards and were purchased from XILONG Scientific, China.

The fresh herbs were provided by Thai Duong Joint Stock Company and were botanically identified by Dr. Do Ngoc Dai Table 1. Specimens of medicinal herbs have been kept and preserved at the Department of Biology of Vinh University.

TABLE 1: LIST OF MEDICINAL HERBS USED IN THIS STUDY

Preparation of the Extraction Residue: The dried medicinal herbs were ground, then soaked in 70% ethanol solvent for 14 days. The 70% ethanol extract was evaporated using a vacuum rotary evaporator under low pressure to obtain the 70% ethanol extract residue. The anti-proliferative activities of the ethanol extract residues were assessed and residues with IC₅₀ values < 100 μg/mL underwent further extraction with n-hexane, ethyl-acetate, and n-butanol solvents. The 70% ethanol extraction residue was completely distributed in distilled water, then subjected to liquid-liquid extraction with the solvents n-hexane, ethyl acetate, and n-butanol, each extraction solvent repeated four times. The extracts of n-hexane, ethyl acetate, n-butanol, and aqueous solution were evaporated using a vacuum rotary evaporator at low pressure to obtain residues n-hexane (H), ethyl acetate (E) extraction, n-butanol (B), and water (W), respectively Table 2.

TABLE 2: EXTRACTION YIELDS OF DIFFERENT SOLVENTS OF HERBS

Cytotoxicity Test: The cytotoxic activities were conducted following the protocol outlined by Monks (1991) ^{7, 8}. The evaluation aimed to determine the total cellular protein content by measuring the optical density (OD) when the cell protein composition was stained with sulforhodamine B (SRB). The OD value, directly proportional to the SRB bound to protein molecules, increased with more cells (more protein). To initiate the test, a solution of the extracted residue or pure compound (10 µL) was diluted in 10% dimethyl sulfoxide (DMSO) and placed in a 96-well tray to create concentrations of 100 µg/mL, 20 µg/mL, 4 µg/mL, 0.8 µg/mL, and 0.16 µg/mL.

Cells, adjusted to a density of 1×10⁵ cells/mL through trypsinization and counting, were added to the test wells (190 µL medium, 6000 cells/well). A separate 96-well tray with cancer cells (190 µL) served as a day 0 control. After 1 hour, the day 0 control cells were fixed with trichloroacetic acid (TCA). Following the growth period in the CO₂ incubator, cells in the test wells were fixed to the well bottom with TCA for 1 hour and stained with 0.4% SRB for 30 minutes at 37 °C. Subsequently, SRB was removed from the test wells, which were then washed three times with acetic acid and air-dried at room temperature. The bound SRB was dissolved using 10 mM unbuffered Tris base, and the protein molecules were stained. After gentle shaking for 10 minutes on a plate shaker, an ELISA Plate Reader (ELx800, BioTek Instruments Inc., Winooski, VT, USA) was employed to read the color content of the SRB dye through the absorption spectrum at 515 nm. The viability of cells in the presence of the extracted residue or pure compound was determined using the formula:

Percentage of cell viability (%) = ([OD (reagent)-OD (day 0)] × 100) / (OD (negative control) - OD (day 0)

The assays were repeated three times for accuracy. Ellipticine served as a positive control and was tested at concentrations of 10 µg/mL, 2 µg/mL, 0.4 µg/mL, and 0.08 µg/mL, while a 10% DMSO solution served as the negative control.

RESULTS: The results of testing the cytotoxicity of the medicinal herbs are presented in Table 3. The 70% ethanol extraction residue of eight medicinal samples including TD.MD1, TD.MD2, TD.MD3, TD.MD11, TD.MD15, TD.MD17, TD.MD20, and TD.MD21 showed anti-proliferative activities with IC₅₀ values ranging from 18.60 to 93.84 µg/mL. The n-hexane, ethyl acetate, n-butanol, and water extract residues of these medicinal herbs demonstrated strong cytotoxic activities against nine cancer cell lines, for NTERA-2 cell line with IC₅₀ values of 8.60 to 90.83 µg/mL Table 4.

TABLE 3: CYTOTOXIC ACTIVITIES (IC₅₀, ΜG/ML) OF 70% ETHANOL EXTRACT RESIDUES OF MEDICINAL HERBS

HepG2: human hepatoma cells; A549: human lung cells; MCF7: human breast cancer cells; HT-29: human colon cancer cells; HeLa: human cervical cancer HeLa cells; RD: Rhabdomyosarcoma (RD) cells; LNCaP: human prostate cancer LNCaP cells; HL-60: human leukemia HL‐60 cancer cell.

TABLE 4: CYTOTOXIC ACTIVITIES (IC₅₀, ΜG/ML) OF DIFFERENT EXTRACT RESIDUES (N-HEXANE, ETHYL ACETATE, N-BUTANOL, WATER) OF MEDICINAL HERBS

H: n-Hexane. E: Ethyl acetate. B: n-butanol. W: water.

DISCUSSION: The aqueous and methanolic extracts of P. urinaria were evaluated for antiproliferative activities against different cancer cell lines, the results indicated that the methanol extract exhibited stronger activities than the water extract ^{3, 9–13}. Several proliferation inhibition mechanisms of P. urinaria extracts have been reported: through inhibition of cellular mobility, invasion, and migration of cells (Saos-2 cell line) ¹⁴; through a mitochondria-associated intrinsic pathway ¹⁵ (Lewis lung carcinoma cells), through a ceramide-related pathway (HL-60 cells, human osteosarcoma 143B cells) ¹³, via activation of Fas/FasL (human osteosarcoma 143B cells) 16; modulation of cell cycle and induces apoptosis through caspase activation in melanoma and prostate cancer cells ¹⁷. The aqueous extract demonstrated a dose-dependent anti-tumor effect at the in-vivo level ¹⁸. The compounds lignan hypophyllanthin, neonirtetralin and helio-buphthalmin lactone demonstrated cytotoxic activities against CHO (Chinese hamster ovary) and J774 (Murine macrophage) cell lines with IC₅₀ values in the range of 6.00–41.30 µM ¹⁹.

In this study, 70% ethanol extract of Solanum trilobatum showed cytotoxic activities with IC50 values of 16.5 to 44.62 µg/mL. The H-TD.MD2 and E-TD.MD2 extracts demonstrated strong proliferation inhibition, whereas the B-TD.MD2 and W-TD.MD2 extracts did not (IC₅₀> 100 µg/mL). The petroleum ether (PE), chloroform (C), ethyl acetate (EA), and ethanol (E) extracts demonstrated cytotoxic activity against the L929 cell line with IC₅₀ values of 7.0, 16.0, 36.0 and 18.5 (µg/mL), respectively ²⁰. Thus, less polar components were responsible for the antiproliferative activities of S. trilobatum. The sobatum compound isolated from petroleum ether extract demonstrated strong cytotoxicity against L929 and Vero cells with LC⁵⁰ values of 7.0 µg and 7.5 µg, respectively ²⁰.

Acetone, chloroform, methanol, and CO2 extracts of A. sinensis all exhibit strong cytotoxic activities. Phthalide compounds are responsible for the antiproliferative activities of Angelica sinensis ^{5, 21, 22}. The compounds n-butylidenephthalide (BLP), senkyunolide A (SKA), and Z-ligustilide (LGT) inhibited the proliferation of HT-29 cell line with IC₅₀ values of 54.17 ± 5.10, 60.63 ± 6.79, and 236.90 ± 18.22 µM, respectively ²³. The compounds riligustilide, tokinolide A, and tokinolide C have shown proliferation inhibitory activities of A549, HCT-8, and HepG2 cell lines with IC⁵⁰ values of 6.79-13.82, 30.92-55.84, and 27.97 -34.34 µM, respectively ²⁴. BLP demonstrated cytotoxic activities against brain tumor cell lines (DBTRG-05MG, GBM8401, GBM8901, G5T/VGH, RG2, SK-N-AS, N18) and other cancer cell lines (A549, B16/F10, J5, PA-1, BCM-1, HL-60) with IC50 values between 15.5 to 67.4 ²⁵. Phthalide compounds have been isolated from extracts of less polar solvents such as n-hexane, pentane, petroleum ether, methanol, 70% ethanol and dichloromethane ²⁶. In this study, the n-hexane extract did not show cytotoxic activities against cancer cell lines, whereas the aqueous extract showed strong activity. The cytotoxic activity of the aqueous extract may have been related to the responsible polysaccharide ²⁷.

The xanthanolide sesquiterpene lactone compounds may have been involved in the cytotoxic activities of X. strumarium. Two compounds, 8-epi-xanthatin and 8-epi-xanthatin epoxide, inhibited the proliferation of cell lines A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) through inhibiting the farnesylation process of human lamin-B by farnesyltransferase ²⁸. Xanthatin fraction (xanthatin and 8-epi-xanthatin) demonstrated anti-proliferative activity of CT26WT cells through interference with the mitotic apparatus with an IC₅₀ value of 8.3 µM ²⁹. Xanthatin and xanthinosin demonstrated cytotoxic activities against WiDr and MDA-MB-231 cell lines with IC₅₀ values of 6.15, 13.9 and 2.65, 4.8, respectively ³⁰. The n-hexane and ethyl acetate extracts in this study showed stronger activities than the n-butanol and water extracts, consistent with previous studies 6–8, which is consistent with the relatively low polarity of sesquiterpene lactone compounds. However, the study of Ly (2021) reported that an ethanolic extract rich in polyphenols exhibited cytotoxic activity against HepG2 cancer cells with an IC₅₀ value of 81.69 μg/mL ³¹.

The free flavones baicalein, wogonin, chrysin, and oroxylin A were isolated from n-butanol extracts that showed significant cytotoxic activity against HepG2, SW480, and MCF7 cells at a concentration of 10 µM32. In the present study, n-butanol and water extracts demonstrated strong cytotoxic activities, while n-hexane and ethyl acetate extracts did not.

The triterpenoid saponin compounds in the roots of P. grandiflorum may be responsible for the antiproliferative activities against cancer cell lines. The platycoside-containing n-butanol fraction of P. grandiflorum inhibited the proliferation of the A549 cancer cell line via autophagy and the modulation of the AMPK/mTOR/AKT and MAPK signaling pathways ³³. The compound platycodin D is the main component in the roots of P. grandiflorum, which has been reported to exhibit time- and concentration-dependent cytotoxic activities ³⁴, on cell lines such as HepG2 (IC₅₀ value of 30 mM at 48 h) ³⁵, BEL-7402 (IC₅₀ values of 37.70±3.99, 24.30±2.30, and 19.70±2.36 μmol/L at 24, 48, and 72 h, respectively.) ³⁶. The extract containing saponin (platycodinD is the main component) was cytotoxic against four cell lines, RWPE-1, RC-59T/h/SA#4, LNCap.FGC, and PC-3,in a dose-dependent manner with IC₅₀ values at 72 h ranging from 28.84 to 45.25 µg/mL. The compounds platycodonoids A and B, platycodin D, deapioplatycodin D, glucopyranosyl platycodigenin, and polygalacin D demonstrated antiproliferative activity against HSC-T6 cells with IC₅₀ values of 5.27, 69.63, 1.77, 8.24, 13.36, and 1.04 μM, respectively ³⁷. The compound lycopodine isolated from the ethanolic extract of L. clavatumca used a decrease in the survival of HeLa cells from 50% to 40% in regard to exposure from 24 h to 48 h at the dose (200 µg/mL)38. The lycopodine inhibited proliferation of PC3 and LnCaP cells with IC₅₀ values of 57.62 and 51.46 µg/mL, respectively ³⁹. The highly-diluted, dynamized homeopathic remedies LC-5C and LC-15C demonstrated their capabilities to induce apoptosis in HeLa cancer cells ⁴⁰. In this present study, the ethyl acetate extract demonstrated the most potent cytotoxic activities compared to the n-hexane and n-butanol extracts, while the aqueous extract did not show any activity. Polar extracts of O. japonicus (75% ethanol extract, methanol extract) have reported proliferative inhibitory activities against many cancer cell lines. Sterol and steroidal saponin components such as ruscogenin, liriopesides B, ophiopogonin B, ophiopogonin D and ruscogenin-1-O-[β-D-glucopyranosyl(1→2)] [β-D-xylopyranosyl (1→3)]-β – D - fucopyranoside (DT-13)  have been reported to be responsible for the cytotoxic activities of O. japonicas ⁴¹. In this present study, ethyl acetate and n-butanol extracts showed strong cytotoxic activities, while n-hexane extracts and aqueous extracts did not show activity.

CONCLUSION: This study evaluated the anti-proliferative activities of 24 Vietnamese traditional medicinal herbs against nine cancer cell lines including HepG2, A549, MCF7, HT-29, Hela, RD, LNCaP, HL-60, and NTERA-2.Eight of them include Phyllanthus urinaria, Solanum trilobatum, Angelica sinensis, Xanthium strumarium, Scutellaria baicalensis, Platycodon grandiflorus, Lycopodium clavatum and Ophiopogon japonicushave shown potential for further research for cancer treatment purposes with IC₅₀ values below 100 µg/mL. There is a need to verify the phytochemical makeup of each of these herbal extracts, to isolate and screen the individual components for activity, and to evaluate the antiproliferative effects and therapeutic dosages in-vivo.

ACKNOWLEDGEMENT: Nil

Data Availability: All data are available upon reasonable request from the corresponding authors Van Khoa Vu, bskhoavd@gmail.com (V.K.V.); Huy Hung Nguyen, nguyenhuyhung@duytan.edu.vn (H.H.N.).

CONFLICTS OF INTEREST: The authors declare no conflict of interest.

REFERENCES:

1. World Health Organization, WHO: https://www.afro.who.int/health-topics/cancer (2024).
2. Burmeister CA, Khan SF, Schäfer G, Mbatani N, Adams T, Moodley J and Prince S: Cervical cancer therapies: Current challenges and future perspectives. Tumour Virus Research 2022; 13: 200238.
3. Glumac PM and LeBeau AM: The role of CD133 in cancer: a concise review. Clinical and Translational Medicine 2018; 7: 1-4.
4. Nga NT, Phuong DT, Cuc NT, Phuong TH, Huong PT, Cuong NX, Huu Tai B, Van Kiem P and Thao DT: Nanoliposomal cercodemasoide A and its improved activities against Ntera-2 cancer stem cells. Natural Product Communications 2020; 15(12): 1934578X20982108.
5. Stern M, Gierse A, Tan S and, Bicker G: Human Ntera2 cells as a predictive in-vitro test system for developmental neurotoxicity. Archives of toxicology 2014; 88: 127-136.
6. Garcia-Oliveira P, Otero P, Pereira AG, Chamorro F, Carpena M, Echave J, Fraga-Corral M, Simal-Gandara J and Prieto MA: Status and challenges of plant-anticancer compounds in cancer treatment. Pharmaceuticals 2021; 14(2): 157.
7. An NT, Chau DT, Huong LT, Van Khoa V, Hung NH, Thao DT, Trang VT, Dai DN and Setzer WN: Lipid peroxidation inhibitory and cytotoxic activities of two Camellia species growing wild in Vietnam. Pharmacognosy Magazine 2023; 19(2): 385-399.
8. Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A and Gray-Goodrich M: Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. Journal of the National Cancer Institute 1991; 83(11): 757-766.
9. Rudin CM, Brambilla E, Faivre-Finn C and Sage J: Small-cell lung cancer. Nature Reviews Disease Primers 2021; 7(1): 3.
10. Rumgay H, Arnold M, Ferlay J, Lesi O, Cabasag CJ, Vignat J, Laversanne M, McGlynn KA and Soerjomataram I: Global burden of primary liver cancer in 2020 and predictions to 2040. Journal of Hepatology 2022; 77(6): 1598-1606.
11. Liu S, Sima X, Liu X and Chen H: Zinc finger proteins: functions and mechanisms in colon cancer. Cancers 2022; 14(21): 5242.
12. Posdzich P, Darr C, Hilser T, Wahl M, Herrmann K, Hadaschik B and, Grünwald V: Metastatic prostate cancer a review of current treatment options and promising new approaches. Cancers 2023; 15(2): 461.
13. Huang ST, Yang RC, Chen MY and Pang JH: Phyllanthus urinaria induces the Fas receptor/ligand expression and ceramide-mediated apoptosis in HL-60 cells. Life Sciences 2004; 75(3): 339-351.
14. Lu KH, Yang HW, Su CW, Lue KH, Yang SF and Hsieh YS: Phyllanthus urinaria suppresses human osteosarcoma cell invasion and migration by transcriptionally inhibiting u-PA via ERK and Akt signaling pathways. Food and chemical toxicology 2013; 52: 193-199.
15. Huang ST, Yang RC, Yang LJ, Lee PN and Pang JH: Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-regulation in Lewis lung carcinoma cells. Life Sciences 2003; 72(15): 1705-1716.
16. Wu HY, Lin TK, Kuo HM, Huang YL, Liou CW, Wang PW, Chuang JH and Huang ST: Phyllanthus urinaria induces apoptosis in human osteosarcoma 143B cells via activation of Fas/FasL‐and mitochondria‐mediated pathways. Evidence‐Based Complementary and Alternative Medicine 2012; 2012(1): 925824.
17. Tang YQ, Jaganath IB and Sekaran SD: Phyllanthus spp. induces selective growth inhibition of PC-3 and MeWo human cancer cells through modulation of cell cycle and induction of apoptosis. PloS one 2010; 5(9): 12644.
18. Huang ST, Yang RC, Lee PN, Yang SH, Liao SK, Chen TY and Pang JH: Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma. International Immunopharmacology 2006; 6(6): 870-879.
19. Van Thanh N, Huong PT, Nam NH, Cuong NX, Thao NP, Dejaegher B, Gordien A, Vander Heyden Y, Quetin-Leclercq J and Van Minh C: A new flavone sulfonic acid from Phyllanthus urinaria. Phytochemistry Letters 2014; 7: 182-185.
20. Mohanan PV and Devi KS: Cytotoxic potential of the preparations from Solanum trilobatum and the effect of sobatum on tumour reduction in mice. Cancer Letters 1996; 110(1-2): 71-76.
21. Yamada Y and Beltran H: The treatment landscape of metastatic prostate cancer. Cancer Letters 2021; 519: 20-29.
22. Anh LH, Lam VQ, Takami A, Khanh TD, Quan NV and Xuan TD: Cytotoxic mechanism of momilactones A and B against acute promyelocytic leukemia and multiple myeloma cell lines. Cancers 2022; 14(19): 4848.
23. Kan WL, Cho CH, Rudd JA and Lin G: Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. Journal of Ethnopharmacology 2008; 120(1): 36-43.
24. Gong W, Zhou Y, Li X, Gao X, Tian J, Qin X and Du G: Neuroprotective and cytotoxic phthalides from angelicae sinensis radix. Molecules 2016; 21(5): 549.
25. Tsai NM, Chen YL, Lee CC, Lin PC, Cheng YL, Chang WL, Lin SZ and Harn HJ: The natural compound n‐butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in-vitro and in vivo3. Journal of Neurochemistry 2006; 99(4): 1251-1262.
26. Chao WW and Lin BF: Bioactivities of major constituents isolated from Angelica sinensis (Danggui). Chinese Medicine 2011; 6: 1-7.
27. Lin PC, Chiou TW and Harn HJ: An evidence-based perspective of Angelica sinensis (Chinese Angelica) for cancer patients. Evidence-based Anticancer Materia Medica 2011; 131-153.
28. Kim YS, Kim JS, Park SH, Choi SU, Lee CO, Kim SK, Kim YK, Kim SH and Ryu SY: Two cytotoxic sesquiterpene lactones from the leaves of Xanthium strumarium and their in-vitro inhibitory activity on farnesyltransferase. Planta Medica 2003; 69(04): 375-377.
29. Piloto-Ferrer J, Sanchez-Lamar A, Francisco M, Gonzalez ML, Merino N, Aparicio G, Perez C, Rodeiro I and Lopes MT: Xanthium strumarium's xanthatins induces mitotic arrest and apoptosis in CT26WT colon carcinoma cells. Phytomedicine 2019; 57: 236-244.
30. Ramírez-Erosa I, Huang Y, Hickie RA, Sutherland RG and Barl B: Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential anticancer agents. Canadian Journal of Physiology and Pharmacology 2007; 85(11): 1160-1172.
31. Ly HT, Truong TM, Nguyen TT, Nguyen HD, Zhao Y and Le VM: Phytochemical screening and anticancer activity of the aerial parts extract of Xanthium strumarium L. on HepG2 cancer cell line. Clinical Phytoscience 2021; 7: 1-8.
32. Ji S, Li R, Wang Q, Miao WJ, Li ZW, Si LL, Qiao X, Yu SW, Zhou DM and Ye M: Anti-H1N1 virus, cytotoxic and Nrf2 activation activities of chemical constituents from Scutellaria baicalensis. Journal of Ethnopharmacology 2015; 176: 475-484.
33. Yim NH, Hwang YH, Liang C and Ma JY: A platycoside-rich fraction from the root of Platycodon grandiflorum enhances cell death in A549 human lung carcinoma cells via mainly AMPK/mTOR/AKT signal-mediated autophagy induction. Journal of Ethnopharmacology 2016; 194: 1060-1068.
34. Xie L, Zhao YX, Zheng Y and Li XF: The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus. Frontiers in Pharmacology 2023; 14: 1148853.
35. Qin H, Du X, Zhang Y and Wang R: Platycodin D, a triterpenoid saponin from Platycodon grandiflorum, induces G2/M arrest and apoptosis in human hepatoma HepG2 cells by modulating the PI3K/Akt pathway. Tumor Biology 2014; 35: 1267-1274.
36. Li T, Xu XH, Tang ZH, Wang YF, Leung CH, Ma DL, Chen XP, Wang YT, Chen Y and Lu JJ: Platycodin D induces apoptosis and triggers ERK-and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells. Acta Pharmacologica Sinica 2015; 36(12): 1503-13.
37. Zhan Q, Zhang F, Sun L, Wu Z and Chen W: Two new oleanane-type triterpenoids from Platycodi radix and anti-proliferative activity in HSC-T6 cells. Molecules 2012; 17(12): 14899-14907.
38. Mandal SK, Biswas R, Bhattacharyya SS, Paul S, Dutta S, Pathak S and Khuda-Bukhsh AR: Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation. European Journal of Pharmacology 2010; 626(2-3): 115-122.
39. Bishayee K, Chakraborty D, Ghosh S, Boujedaini N and Khuda-Bukhsh AR: Lycopodine triggers apoptosis by modulating 5-lipoxygenase, and depolarizing mitochondrial membrane potential in androgen sensitive and refractory prostate cancer cells without modulating p53 activity: signaling cascade and drug–DNA interaction. European Journal of Pharmacology 2013; 698(1-3): 110-121.
40. Samadder A, Das S, Das J, Paul A, Boujedaini N and Khuda-Bukhsh AR: The potentized homeopathic drug, Lycopodium clavatum (5C and 15C) has anti-cancer effect on hela cells in-vitro. Journal of Acupuncture and Meridian Studies 2013; 6(4): 180-187.
41. Liu Q, Lu JJ, Hong HJ, Yang Q, Wang Y and Chen XJ: Ophiopogon japonicus and its active compounds: A review of potential anticancer effects and underlying mechanisms. Phytomedicine 2023; 113: 154718.
    

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    How to cite this article:

    Vu VK, Nguyen TGA, Dao TMC, Le TH, Do TT, Nguyen NH, Nguyen THL, Nguyen HT, Nguyen THV, Do ND, Nguyen HH and Setzer WN: Anti-proliferative activities of Vietnamese herbs. Int J Pharmacognosy 2025; 12(3): 240-47. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.12(3).240-47.

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