I am looking for manga (or maybe anime) where female character (preferably MC but side kick, love interest, antagonist, side character work too) goes through lots of struggles, faces tragedy or terrible consequences, is forced to shoulder some kind of responsibility, has her morality challenged, compromised, etc. I am fine with psychological hurdles, but added physical damage and challenges are preferable. Any genre and rating is fine.

Assuming you don't mind NO happy endings...
Suna no Shiro
Deep Love - Ayu no Monogatari
Dokuhime
Satougashi no Dangan wa Uchinukenai

~4400 manga completed
~1700 ongoing...

Thanks.