Anti-proliferative and apoptotic effects of chamomile extract in various human cancer cells

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Chamomile (Matricaria chamomilla), one of the most popular herbs, known for centuries for its medicinal values is consumed in the form of tea equivalent to over one million cups per day. Aqueous standardized extract of chamomile contains ~1.2% apigenin and 0.5% essential oils. Chamomile has been valued as a relaxant for digestion and nerves and frequently used as a mild sedative to calm nerves and reduce anxiety. It has many reported medicinal uses against skin irritation, inflammation, sore gums and general wound healing.Other proven actions of the herb include anti-ulcer, anti-bacterial, liver stimulation and anti-mycotic effects. Apart from its broad spectrum medicinal use, the anticancer properties of chamomile have not been evaluated. Here we assessed the anticancer properties of chamomile against various human cancer cell lines. Dry flower powder (~ 1 g) was subjected to aqueous and methanolic extraction, freeze dried, sterilized and used for cell culture. Exposure of cells with methanolic chamomile extract caused minimal growth inhibitory responses in normal human prostate epithelial cells (PrEC) and virally transformed normal human prostate epithelial cells (PZ-HPV-7). In sharp contrast, chamomile treatment resulted in significant decrease in cell viability in various human cancer cell lines. The IC50 values after 72 h chamomile exposure to human prostate cancer cells, LNCaP, DU145 and PC-3 ranged between 100-200 μg/mL. The IC50 values for aqueous chamomile extract ranged from 1500-3000 μg/mL. Similar growth inhibitory responses were observed in other human cancer cell lines viz. HeLa (cervical adenocarcinma), RKO (colon carcinoma), T-47D (breast carcinoma), and HT1080 (fibrosarcoma) after chamomile treatment. Chamomile exposure resulted in significant apoptosis in all prostate cancer cell lines as evident from (i) DNA fragmentation, (ii) fluorescence microscopy, and (iii) cell death detection ELISA. Further, pure apigenin and its analogues viz. apigenin-7-glucoside, apigenin-7-O-neohespiridoside and apiin were evaluated for their anti-proliferative properties in cancer cells. Amongst the agents tested, apigenin was most effective in inhibiting prostate cancer cell growth (IC50 at 24 h, 12-50 μg/mL) followed by apigenin-7-glucoside (IC50 at 24 h, 125-150 μg/mL), whereas apigenin-7-O-neohespiridoside and apiin exhibited weak responses in cancer cells. HPLC analysis of aqueous and methanolic chamomile extract confirmed apigenin-7-glucoside as the major constituents of chamomile, whereas some minor components were also observed. This study represents the first observation demonstrating the anticancer effects of chamomile and warrants detailed investigation on its mechanism of action to translate this herbal remedy for its use in cancer patients. (Grant support: USPHS grants NCCAM RO1 AT002709 and NIH RO1CA1085)