Study in mice and human cells describes reactivation of an important tumour suppressive gene using a vegetable extract thus offering a promising strategy for kansa matibabu
Kansa ni chanzo cha pili cha vifo duniani kote. Katika saratani, mabadiliko mengi ya kijenetiki na epijenetiki ama ya kurithiwa au kupatikana kimaumbile. Mabadiliko haya yanayohusika katika ukuzaji wa saratani ni ya aina mbili tofauti - (a) kuwezesha au 'kupata utendakazi' wa onkojeni za seli na (b) kuzima au 'kupotea kwa utendaji kazi' wa jeni za kukandamiza uvimbe. Tumor jeni za kukandamiza kawaida huzuia kuenea kwa seli na ukuaji wa tumor. Iwapo zitazimwa, vidhibiti hasi vya kuenea kwa seli hupotea na hii inachangia kuenea kwa seli zisizo za kawaida za tumor. Uanzishaji upya wa vikandamizaji vya tumor kama mkakati unaowezekana wa matibabu ya wanadamu saratani imefanyiwa utafiti lakini haijachunguzwa kwa undani kama tafiti za kuzuia protini za oncogenic.
A potent tumour suppressive gene called PTEN is the most commonly mutated, deleted, down-regulated or silenced gene in human cancers. PTEN is a phosphatase which is active as a dimer at the plasma membrane. If PTEN mutations are inherited then it can cause syndromes like susceptibility to kansa and developmental defects. Tumour cells exhibit low levels of PTEN. Restoration of normal levels of PTEN in cancer cells can allow PTEN gene to continue its tumour suppressive activity. It is known that PTEN dimer formation and its recruitment at the membrane is critical for its function, however, the exact molecular mechanisms of this are still unknown.
Utafiti uliochapishwa katika Bilim tarehe 17 Mei 2019 inafafanua njia mpya inayohusisha PTEN ambayo hutumika kama kidhibiti cha udhibiti wa ukuaji wa uvimbe na ni muhimu kwa maendeleo ya saratani. Watafiti walichunguza jeni inayoitwa WWP1 ambayo inajulikana kuwa na jukumu muhimu katika maendeleo ya saratani na huzalisha kimeng'enya cha ubiquitin E3 ligase. Kimeng'enya hiki ni protini inayoingiliana ya PTEN ambayo huzuia shughuli ya kukandamiza uvimbe ya PTEN kwa kukandamiza dimerization ya PTEN, uajiri wa utando na hivyo utendakazi wake. WWP1 imeongezwa kinasaba katika saratani nyingi zikiwemo matiti, tezi dume na ini. Baada ya kuchunguza muundo wa enzyme hii ya 3-dimensional, watafiti waliorodhesha molekuli ndogo iitwayo indole-3-carbinol (I3C) ambayo inaweza kuzuia shughuli ya kimeng'enya hiki. I3C, kiwanja cha asili, ni kiungo cha broccoli na cruciferous nyingine mboga ambayo ni pamoja na cauliflower, kabichi, kale na brussels sprouts. Inajulikana kuwa mboga kama hizo ni nyongeza nzuri kwa lishe ya mtu na pia matumizi yake hapo awali yalihusishwa na kupungua kwa hatari ya saratani.
The compound I3C was administered to cancer prone mice (mouse model of prostate kansa) and into human cell lines and it was seen that I3C inhibited activity of WWP1 by depleting it. This led to restored tumour suppressive power of PTEN. I3C is thus a natural pharmacological inhibitor of WWP1 which can trigger PTEN reactivation. WWP1 appeared to be a direct MYC target gene (protooncogene) for MYC driven tumorigenesis or formation of tumours. The study showed that perturbation of WWP1 is enough to restore PTEN’s tumour suppression activity.
It may not be feasible to achieve these anti-cancer benefits from simply consuming broccoli and other cruciferous vegetables as food since very high levels of daily consumption would be needed. Further investigations need to focus on studying functions of WWP1 and developing its inhibitors as the current study establishes that inhibition of WWP1-PTEN pathway is promising when there is presence of tumour-driven MYC overexpression or abnormal PTEN function. The current study paves a way for a new kansa treatment using tumour suppressor reactivation approach.
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Chanzo (s)
Lee Y. et al. 2019. Uwezeshaji upya wa kikandamiza uvimbe cha PTEN kwa matibabu ya saratani kupitia kuzuiwa kwa njia ya kizuizi ya MYC-WWP1. Sayansi, 364 (6441). https://doi.org/10.1126/science.aau0159
