Asteriscus graveolens Extract in Combination with Cisplatin/Etoposide/Doxorubicin Suppresses Lymphoma Cell Growth through Induction of Caspase-3 Dependent Apoptosis

Abstract

Chemotherapy drugs action against cancer is not selective, lead to adverse reactions and drug resistance. Combination therapies have proven more effective in defeating cancers. We hypothesize that plant extract/fraction contains many/several compounds and as such can target multiple pathways as cytotoxic agent and may also have chemo sensitizing activities. We designed a study in which, Asteriscus graveolens (Forssk.) Less (A. graveolens)-derived fraction that contains sesquiterpene lactone asteriscunolide isomers (AS) will be tested in combination with known chemotherapy drugs. Successful combination will permit to reduce chemotherapy drugs concentration and still get the same impact on cancer cells. Sesquiterpene lactone such as asteriscunolide isomers is a naturally occurring compound found in a variety of fruits, vegetables, and medicinal plants with anti-cancer properties. The experiments presented here showed that adding plant fraction containing AS permit reducing the concentration of cisplatin/etoposide/doxorubicin in order to reduce mouse BS-24-1 lymphoma cells (BS-24-1 cells) survival. It involved enhancing the production of Reactive Oxygen Species (ROS), activation of caspase-3 and inhibition of Topoisomerase I activity. Taken together, the results suggest that A. graveolens fraction sensitized BS-24-1 cells to cisplatin/etoposide/doxorubicin through induction of ROS and caspase-3-dependent apoptosis.

An Extract of Transgenic Senna obtusifolia L. hairy roots with Overexpression of PgSS1 Gene in Combination with Chemotherapeutic Agent Induces Apoptosis in the Leukemia Cell Line

“…Many studies have examined the potential for plant-derived biologically-active compounds to induce apoptosis in cancer cells, with very promising results being obtained by the combination of the extract with a synthetic anti-cancer drug [51][52][53][54][55]. One such commonly-used anti-cancer agent is doxorubicin which is commonly used in the treatment of a wide range of cancers, including, different types of carcinomas or hematological malignancies.…”

Antifungal, Antitumoral and Antioxidant Potential of the Danube Delta Nymphaea alba Extracts

“…Combination therapies have proven to be promising alternatives for cancer therapy. As previously described [44], plant extracts contain several beneficial compounds that can target multiple pathways in cancer cells and can be more selective, sparing the normal cells. In addition, such combinations will enable a reduction in the dose of chemotherapy drugs.…”

Chemo‐Geographic Variations in Wild Population of Asteriscus graveolens in Israel Based on Volatile Composition Analyses

“…[5,20] Previous studies reported anticancer activity of asteriscunolides in human cell lines [21] and mouse cell lines. [14,15] Other compounds that were identified in the current research that also derived from the humulene skeleton are: bisabolone, 6-hydroxybisabol-2-en-1-one, germacrene-D, humulene-epoxide-II and α-humulene ( Table 1). [10] The high abundance of humulene derivatives in A. graveolens plants makes this species potentially pharmaceutically appropriate.…”

“…[1,6,13] A. graveolens methyl tert-butyl ether (MTBE) extraction was tested for anticancer activity and found to be selectively cytotoxic to tumor cell lines in mice, but not to non-cancerous cells. [14,15] The postulated mechanism is stimulation of reactive oxygen species (ROS) activity followed by induction of apoptosis. [14,15] The plethora of therapeutic and antimicrobial activities of A. graveolens make it a promising plant candidate for further pharmacological and agricultural inquiries.…”

“…[14,15] The postulated mechanism is stimulation of reactive oxygen species (ROS) activity followed by induction of apoptosis. [14,15] The plethora of therapeutic and antimicrobial activities of A. graveolens make it a promising plant candidate for further pharmacological and agricultural inquiries. Hence, the present study aimed to characterize the volatiles profile of A. graveolens ecotypes growing in Israel and the chemical variability within these populations.…”