Show simple item record

AuthorAkhtar, Sabah
AuthorAchkar, Iman W
AuthorSiveen, Kodappully S
AuthorKuttikrishnan, Shilpa
AuthorPrabhu, Kirti S
AuthorKhan, Abdul Q
AuthorAhmed, Eiman I
AuthorSahir, Fairooz
AuthorJerobin, Jayakumar
AuthorRaza, Afsheen
AuthorMerhi, Maysaloun
AuthorElsabah, Hesham M
AuthorTaha, Ruba
AuthorOmri, Halima El
AuthorZayed, Hatem
AuthorDermime, Said
AuthorSteinhoff, Martin
AuthorUddin, Shahab
Available date2019-05-15T07:35:57Z
Publication Date2019-05-05
Publication NameFrontiers in Oncologyen_US
Identifierhttp://dx.doi.org/10.3389/fonc.2019.00285
CitationAkhtar S, Achkar IW, Siveen KS, Kuttikrishnan S, Prabhu KS, Khan AQ, Ahmed EI, Sahir F, Jerobin J, Raza A, Merhi M, Elsabah HM, Taha R, Omri HE, Zayed H, Dermime S, Steinhoff M and Uddin S (2019) Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling. Front. Oncol. 9:285. doi: 10.3389/fonc.2019.00285
ISSN2234-943X
URIhttp://hdl.handle.net/10576/11556
AbstractSanguinarine (SNG), a benzophenanthridine alkaloid, has displayed various anticancer abilities in several vivo and studies. However, the anticancer potential of SNG is yet to be established in multiple myeloma (MM), a mostly incurable malignancy of plasma cells. In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppression of the constitutively active STAT3 with a concomitant increase in expression of protein tyrosine phosphatase (SHP-1). SNG treatment of MM cells leads to down-regulation of the anti-apoptotic proteins including cyclin D, Bcl-2, Bclxl, and XIAP. In addition, it also upregulates pro-apoptotic protein, Bax. SNG mediated cellular DNA damage in MM cell lines by induction of oxidative stress through the generation of reactive oxygen species and depletion of glutathione. Finally, the subtoxic concentration of SNG enhanced the cytotoxic effects of anticancer drugs bortezomib (BTZ) by suppressing the viability of MM cells via induction of caspase-mediated apoptosis. Altogether our findings demonstrate that SNG induces mitochondrial and caspase-dependent apoptosis, generates oxidative stress, and suppresses MM cell lines proliferation. In addition, co-treatment of MM cell lines with sub-toxic doses of SNG and BTZ potentiated the cytotoxic activity. These results would suggest that SNG could be developed into therapeutic agent either alone or in combination with other anticancer drugs in MM.
Languageen
PublisherFrontiers Media
SubjectSTAT3
Subjectapoptosis
Subjectcaspases
Subjecthematological malignancy
Subjectmultiple myeloma
Subjectsanguinarine
TitleSanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling.
TypeArticle
Volume Number9


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record