Bisphosphonates are stable analogue

Bisphosphonates are stable analogues of pyrophosphate. The more potent bisphosphonates in routine use all contain a nitrogen atom in the R2 side-chain attached to the geminal carbon in the P-C-P backbone, and are known as the ‘nitrogen-containing bisphosphonates’ (N-BPs). The presence of the nitrogen atom increases their potency and enables them to act in the mevalonate pathway of cholesterol biosynthesis by selectively inhibiting the key enzyme, farnesyl pyrophosphate synthase (FPPS) [1]. Inhibition of FPPS leads to a diminished post-translational prenylation of small GTPase proteins, including signalling molecules such as monomeric G proteins of the Ras and Rho families.
When their expression and activation escape the control mechanisms, small GTPases play an essential part in promoting tumorigenesis and tumour metastasis [2–5] and their inactivation could have anti-tumoral effects.
Indeed, growth of human colon cancer cells can be inhibited by N-BPs [6, 7]. Furthermore, N-BPs are known to stimulate gamma delta (γδ)- T cells which cause the acute phase response often seen when they are given parenterally, and this in turn may induce anti-tumour properties [8]. For these reasons, we postulated that orally administered N-BPs might have local anti-neoplastic actions in the colon.

Hasil (Bahasa Indonesia) 2:

Bifosfonat merupakan analog stabil pirofosfat. Bifosfonat lebih kuat dalam penggunaan rutin semua mengandung atom nitrogen dalam R2 sisi-rantai terikat pada atom karbon geminal di backbone PCP, dan dikenal sebagai 'mengandung nitrogen bifosfonat' (N-BPs). Kehadiran atom nitrogen meningkatkan potensi mereka dan memungkinkan mereka untuk bertindak dalam jalur mevalonat dari biosintesis kolesterol secara selektif menghambat enzim kunci, farnesyl pirofosfat sintase (FPPS) [1]. Penghambatan FPPS mengarah ke prenilasi pasca-translasi berkurang protein GTPase kecil, termasuk molekul sinyal seperti protein G monomer dari Ras dan Rho keluarga.
Ketika ekspresi dan aktivasi mereka melarikan diri mekanisme kontrol, GTPases kecil memainkan bagian penting dalam mempromosikan tumorigenesis dan metastasis tumor [2-5] dan inaktivasi mereka bisa memiliki efek anti-tumoral.
Memang, pertumbuhan sel kanker usus besar manusia dapat dihambat oleh N-BPs [6, 7]. Sifat anti-tumor sel T yang menyebabkan respon fase akut sering terlihat ketika mereka diberikan secara parenteral, dan ini pada gilirannya dapat menyebabkan [8] - Selanjutnya, N-BPs dikenal untuk merangsang delta gamma (γδ). Untuk alasan ini, kita mendalilkan bahwa oral N-BPs mungkin memiliki tindakan anti-neoplastik lokal di usus besar.