Antiproliferative Activity of (-)-Rabdosiin Isolated from Ocimum sanctum L.

Background: Ocimum sanctum L. (holy basil; Tulsi in Hindi) is an important medicinal plant, traditionally used in India. Methods: The phytochemical study of the nonpolar (dichloromethane 100%) and polar (methanol:water; 7:3) extracts yielded fourteen compounds. Compounds 6, 7, 9, 11, 12, and 13, along with the methanol:water extract were evaluated for their cytotoxicity against the human cancer cell lines MCF-7, SKBR3, and HCT-116, and normal peripheral blood mononuclear cells (PBMCs). Results: Five terpenoids, namely, ursolic acid (1), oleanolic acid (2), betulinic acid (3), stigmasterol (4), and ß-caryophyllene oxide (5); two lignans, i.e., (-)-rabdosiin (6) and shimobashiric acid C (7); three flavonoids, luteolin (8), its 7-O-ß-D-glucuronide (9), apigenin 7-O-ß-D-glucuronide (10); and four phenolics, (E)-p-coumaroyl 4-O-ß-D-glucoside (11), 3-(3,4-dihydroxyphenyl) lactic acid (12), protocatechuic acid (13), and vanillic acid (14) were isolated. Compound 6 was the most cytotoxic against the human cancer lines assessed and showed very low cytotoxicity against PBMCs. Conclusions: Based on these results, the structure of compound 6 shows some promise as a selective anticancer drug scaffold.

Selective cytotoxicity of the herbal substance acteoside against tumor cells and its mechanistic insights.

Natural products are characterized by extreme structural diversity and thus they offer a unique source for the identification of novel anti-tumor agents. Herein, we report that the herbal substance acteoside being isolated by advanced phytochemical methods from Lippia citriodora leaves showed enhanced cytotoxicity against metastatic tumor cells; acted in synergy with various cytotoxic agents and it sensitized chemoresistant cancer cells. Acteoside was not toxic in physiological cellular contexts, while it increased oxidative load, affected the activity of proteostatic modules and suppressed matrix metalloproteinases in tumor cell lines. Intraperitoneal or oral (via drinking water) administration of acteoside in a melanoma mouse model upregulated antioxidant responses in the tumors; yet, only intraperitoneal delivery suppressed tumor growth and induced anti-tumor-reactive immune responses. Mass-spectrometry identification/quantitation analyses revealed that intraperitoneal delivery of acteoside resulted in significantly higher, vs. oral administration, concentration of the compound in the plasma and tumors of treated mice, suggesting that its in vivo anti-tumor effect depends on the route of administration and the achieved concentration in the tumor. Finally, molecular modeling studies and enzymatic activity assays showed that acteoside inhibits protein kinase C. Conclusively, acteoside holds promise as a chemical scaffold for the development of novel anti-tumor agents.

Polar constituents of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) and their cytotoxic/cytostatic activity.

The methanol extract of the aerial parts of Marrubium thessalum Boiss. & Heldr. (Lamiaceae) afforded 30 phenolic metabolites, belonging to the classes of phenylethanoid glycosides, flavonoids and simple phenolic compounds. The crude methanol extract as well as the secondary metabolites were screened for their cytotoxic/cytostatic effects against four human cancer cell lines, specifically HeLa, MCF-7, FM3 and HCT-116 and demonstrated considerable cell growth-inhibitory activity. The differential cytotoxicity of the compounds implied possible structure-activity relationships. Selected compounds were evaluated for their toxicity against human peripheral blood mononuclear cells, where some of them showed marginal toxic effects. The results suggest that M. thessalum produces secondary metabolites that demonstrate selective anticancer activity concomitantly with reduced toxicity on lymphocytes. The structure of such compounds can eventually lead to the development of novel pharmaceutical agents.