Differential effects of thymoquinone on lysophosphatidic acid-induced oncogenic pathways in ovarian cancer cells
| Autor: | Muralidharan Jayaraman, Danny N. Dhanasekaran, Ji Hee Ha, Rangasudhagar Radhakrishnan, Ciro Isidoro, Mingda Yan, Yong Sang Song, Rohini Gomathinayagam |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
endocrine system diseases
medicine.medical_treatment 0211 other engineering and technologies lcsh:Medicine 02 engineering and technology Phytochemical 01 natural sciences chemistry.chemical_compound Ovarian cancer 021105 building & construction Lysophosphatidic acid medicine Thymoquinone Tumor microenvironment Chemistry Cell growth Growth factor lcsh:R Cell migration medicine.disease 0104 chemical sciences LPA 010404 medicinal & biomolecular chemistry Anticancer Complementary and alternative medicine Cancer research lipids (amino acids peptides and proteins) Signal transduction |
| Zdroj: | Journal of Traditional and Complementary Medicine, Vol 10, Iss 3, Pp 207-216 (2020) Journal of Traditional and Complementary Medicine |
| ISSN: | 2225-4110 |
| Popis: | Thymoquinone, a therapeutic phytochemical derived from Nigella sativa, has been shown to have a potent anticancer activity. However, it has been identified that the tumor microenvironment (TME) can attenuate the anticancer effects of thymoquinone (TQ) in ovarian cancer. Lysophosphatidic acid (LPA), a lipid growth factor present in high concentration in the TME of ovarian cancer, has been shown to regulate multiple oncogenic pathways in ovarian cancer. Taking account of the crucial role of LPA in the genesis and progression of ovarian cancer, the present study is focused on assessing the efficacy of TQ in inhibiting LPA-stimulated oncogenic pathways in ovarian cancer cells. Our results indicate that TQ is unable to attenuate LPA-stimulated proliferation or metabolic reprogramming in ovarian cancer cells. However, TQ potently inhibits the basal as well as LPA-stimulated migratory responses of the ovarian cancer cells. Furthermore, TQ abrogates the invasive migration of ovarian cancer cells induced by Gαi2, through which LPA stimulates cell migration. TQ also attenuates the activation of JNK, Src, and FAK, the downstream signaling nodes of LPA-LPAR-Gαi2 signaling pathway. In addition to establishing the differential effects of TQ in ovarian cancer cells, our results unravel the antitherapeutic role of LPA in the ovarian cancer TME could override the inhibitory effects of TQ on cell proliferation and metabolic reprogramming of ovarian cancer cells. More importantly, the concomitant finding that TQ could still sustain its inhibitory effect on LPA-stimulated invasive cell migration, points to its potential use as a response-specific therapeutic agent in ovarian cancer. Graphical abstract Image 1 Highlights • LPA, present in the TME of ovarian cancer, plays a determinant role in limiting the anti-oncogenic efficacy of TQ. • TQ has no inhibitory effect on LPA-stimulated oncogenic cell proliferation and metabolic reprogramming. • However, TQ potently inhibits both the basal and LPA- or the downstream Gαi2-induced invasive migration ovarian cancer cells. • Corollary to these findings, TQ also inhibits JNK, Src, and FAK that are involved in LPA-induced invasive cell migration. • These findings identify the potential of TQ as a response-specific therapeutic phytochemical in vivo. |
| Databáze: | OpenAIRE |
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